Sunday, December 6, 2009

Two new Studies: Part I - Co-infections point to three strikes theory

A follow-up study was done by Dr. Kerr, demonstrating that ME/CFS symptoms are not caused by XMRV alone, but that co-infections have various additive symptoms - leading more credence to what I call a three strikes theory. For ME/CFS to develop, you need the following three conditions to develop in a more/less orderly sequence:

Infection with XMRV

Co-infection with another etiological agent: various herpesviruses, certain bacteria

Major immune challenge: Influenza, surgery, immunosupression

The basis of this research is that Dr. Kerr separated various CFS cohorts based on symptoms, and tested various consistent immunological disturbances based on certain pathogens present. There was a definitive correlation between the severity of symptoms, and the type of infection present. The four pathogens tested were: Eppstein-barr virus, enterovirus, parvovirus B19, and the bacterium coxiella burnetii. In the test, a study was done looking at the differential expression of 88 genes. There was also a regional difference in CFS subtype patterns: Birmingham, Bristol, Leicester, London, New York, and Dorset.

Here are my conclusions without getting into too much detail: even though EBV, Parvovirus B19, and Enterovirus have been fingered as triggering ME/CFS, it clearly tells me that they are not the cause. ME/CFS has often been described as a heterogenous ailment of many possible causes: a theory that existed in AIDS patients before the discovery of HIV. I believe that ME/CFS, FMS, and Gulf War syndrome bear a single unified cause, and that cause is XMRV.

XMRV is the first strike: without XMRV or closely related retroviruses you can't have ME/CFS. If XMRV infects a normal individual, I am of the opinion that a healthy immune system can keep the virus in check for many, many years. Over time, XMRV leads to an immune dysfunction syndrome, though not a severe life-threatening immune deficiency syndrome like AIDS. XMRV is the mastermind.

The second stage, which I call the second strike, is what sets the stage for ME/CFS. Throughout a lifetime, most of us will become infected with multiple persistent herpesviruses: EBV, HHV-6, Cytomegalovirus, Herpes Simplex... yet a healthy immune system can keep them in check. At this stage, most XMRV infected individuals will probably remain asymptomatic. The body now struggles to maintain the immune system at equilibrium, and it might take longer to recover from simple viruses like the common cold, and some patients might exhibit sub-clinical signs of ME/CFS. The pathogen in this case plays the role of accomplice.

The third stage I will loosely call the third strike - the event that initiates ME/CFS I believe requires a period of prolonged immune activation, or inversely immunosuppression. At this point, the immune system is ill-prepared to fight a war on another front. In comes a pathogen that causes a vigorous and prolonged immune response such as a bacterial infection, or influenza, and now the immune response is mobilized towards it, retreating from the two previously acquired infections: the viral burden initiates a chain reaction within immune cells. XMRV viral load spikes, leading to the destruction of NK cells, and pathogens like EBV now seize the day, and begin replicating, and viruses like EBV can now cause immune downregulation, slowing the creation of new NK cells from progenitor stem cells, capable of arresting EBV.

Conclusion: ME/CFS, FMS, and Gulf war syndrome are caused by a common pathogen, which causes a common set of symptoms, and the heterogenous cluster of symptoms can be explained by co-infections with other pathogens.

Historically, blood samples from Dorset used in Kerr's studies have come from patients attending the Dorset CFS Service (co-author Selwyn Richards, rheumatologist, is lead CFS consultant for Dorset).

There is a bitter irony, here, as the Dorset CFS Service, touted as a model of good service provision when the CFS clinics were being developed several years ago, offers those referred to the service little more than a course of OT led, weekly two hour sessions of group CBT.

"I'm assuming "major immune challenge" could also mean some vaccines?"

As someone who is 100% disabled with cfids, I know of no one in the small group of people dealing with this who report having a vaccine shortly prior to onset. For one person the final insult strongly appears to be occupational exposure to high concentrations of glues/solvents without the required breathing mask. This was an exposure 100s of times higher than from living in, say, a polluted area in the US. Autism is extremely different from cf, me, and Gulf War illness; it seems unlikely that a standard vaccine set causes autism in some people and cf/me in others. None of these illnesses show a close linkage in time with the introduction of modern vaccination over half a century ago.

Many things can cause a body to malfunction, possibly including vaccines, but those seem to have become an all-purpose popular scapegoat for a wide variety of conditions. Perhaps our having fewer infectious diseases in the environment due to common vaccination series is reducing immune stress in general and preventing worse outcomes from XMRV + other unknown stresses. Perhaps vaccines have risks we don't know of since we haven't turned over the right rock, but they do have real and large benefits. Nothing is totally safe; I think we in the US need to distinguish between likely risks vs the rare but sensational.

@Suzy Chapman: Thank you for that valuable information. Us folks with severe CF do not have enough functional hours to learn the tangled story of this condition, and almost no hours with the level of cognitive function required to parse scientific results. We depend on people such as yourself to make the facts known.

It is entirely possible that vaccines, especially multiple childhood vaccines given on a SINGLE day (each containing a different adjuvant/immunostimulator) reactivate a retrovirus such as XMRV and/or cause its spread through CNS…

Another thing to note is that vaccination with live vaccine viruses is often contraindicated in immuno-suppressed. There is a very good recent Cochrane Review paper discussing MMR vaccine in HIV positive, calling for caution in cases when immune cell counts are under a certain level because of a VERY REAL danger of vaccine virus establishing permanency in the host. (and possibly serving as Stage 2. or 3. cofactor in the above hypothesis of “triple hit”). There is also an “interesting” study out there showing presence of vaccine strain of polio virus in HIV positive children, long after vaccination (cue the demonised Wakefield et al findings showing presence of vaccine strain measles virus in children with autism). If indeed there is a XMRV link in autism there is a very real possibility of underlying immune suppression giving way to such an event.

References to studies observing retroviral reactivation following vaccinations, and those showing risks of live virus vaccinations in immunosupressed hosts can be found here http://tinyurl.com/y9lsptp

About Me

My name Dr. Timothy Luckett. I hold an undergraduate degree in Biochemistry from Newcastle Unversity, an Msc in Biochemistry from University of Alberta, PhD in Cellular and Molecular Biology from Cambridge University, and I have worked for the CDC as a postdoctoral fellow, and worked for Orchestra Therapeutics, until their insolvency last year. My research interests is retroviruses - which was an area of active research at Orchestra Therapeutics. The recent discovery of XMRV as a potential link to Chronic Fatigue Syndrome has become very much of a research interest of mine, as my younger sister is has struggled with the disorder since the age of 19. Since my departure from Orchestra Therapeutics, I am now back in the UK, awaiting a faculty position at a university.